Therapeutic potential of platelet-activating factor antagonism in the management of myocardial infarction

BACKGROUND: Antagonists of platelet-activating factor (PAF) reduce myocardi al postischemia reperfusion injury when given before the onset of ischemia. However, the effects of PAF antagonists when administered at a clinically modelled time (during ischemia but before reperfusion) are controversial. M oreover, the extended survival (eight day) and the characteristics of scar formation after treatment with PAF antagonists have not been investigated. OBJECTIVES: To determine the therapeutic potential of PAF antagonist TCV-30 9 for the treatment of regional myocardial ischemia-reperfusion injury; and to determine the effects of TCV-309 on cardiovascular recovery, evolution of scar formation and survival eight days after a myocardial infarction tre ated with reperfusion. ANIMALS AND METHODS: Swine underwent regional myocardial ischemia for 60 mi ns by ligation of the left anterior descending coronary artery, followed by reperfusion for eight days. The treated group (n=7) received PAF antagonis t TCV-309 (0.1 mg/kg) 45 mins after ligation; the untreated group (n=7) rec eived vehicle only. RESULTS: Untreated animals experienced significantly (P<0.001) lower system ic arterial blood pressure during the reperfusion period than animals treat ed with TCV-309. Furthermore, untreated animals required significantly more (P<0.01) antiarrhythmic and inotropic support. Only two of seven animals i n the untreated group survived, which was significantly different (P<0.05) from the six of seven treated animals that survived for eight days. Morphom etric analyses did not show differences between groups in the characteristi cs of scar formation following reperfusion for eight days. CONCLUSIONS: PAF antagonist TCV-309 improves survival and reduces cardiovas cular dysfunctions associated with regional myocardial ischemia reperfusion injury when administered at a clinically modelled time.